The T cell surface glycoprotein CD4 is not only a receptor for antigen recognition and immune system activation, but also the receptor for the human immunodeficiency virus (HIV). Studies have shown that the presence of CD4 is not only necessary but sufficient to render cells susceptible to HIV infection. Several recent reports have also demonstrated that soluble CD4 is able to selectively inhibit and neutralize HIV binding and infection of CD4+ cells. Glycosylation of some glycoproteins has been shown to be required for their processing and transport to the cell surface. The primary sequence of CD4 indicates two potential glycosylation sites. A recent report utilizing tunicamycin to block glycosylation of T4+ cells suggests that glycosylation is necessary for cell surface expression of the receptor. We have used site-directed mutagenesis to create a series of mutants incapable of glycosylation at one or both sites. These mutants were placed under the control of the SV 40 late promotor and transfected and expressed in COS 1 cells. By this analysis we were able to show that both glycosylation sites are utilized in the expression of CD4. Additionally we have constructed a truncated mutant of CD4 lacking the transmembrane and cytoplasmic portions which will be used in overexpression of the protein for further structure-function analysis.